The literature is replete with the use of zinc compounds as a source for a physiologically active zinc ion in mouthwashes, rinses, toothpastes and dentifrices. Zinc has been used most often for its ability to meliorate oral malodor (bad breath). Additionally, zinc compounds have been utilized as astringent-desensitizing agents. It has also been proposed by those skilled in the art that the zinc ion has anticalculus and antiplaque properties. The attempted formulation of stable, biologically active zinc containing products has, however, met with problems.
Highly ionized and soluble zinc salts, such as zinc chloride, provide the best source of zinc ions having the greatest bioavailability. However, zinc chloride in aqueous solution over time tends to form oxychlorides and zinc hydroxides. These byproducts all have low solubility and result in cloudy, unaesthetic solutions. Therefore, in an attempt to maintain clear, stable solutions of zinc compounds, the following approaches have been taken by those skilled in this art.
The pH of the conventional zinc chloride solution has been lowered to less than 4.5 through the use of mineral or organic acid buffers in an attempt to provide a clear, stable solution. This technique suffers, however, from the fact that the final products have severe astringency and an unacceptably sour taste.
The use of certain zinc salts such as zinc phenolsulfonate, as disclosed in U.S. Pat. No. 4,022,880, or carboxymethylsuccinate, as disclosed in U.S. Pat. No. 4,144,323, which tend to be stable at a higher pH than other zinc salts, has also been proposed.
Sparingly soluble salts such as zinc citrate, have been used to slow down the release of zinc ions thereby reducing astringency and presumably providing a sustained level of in-vivo activity and increased formula stability.
The use of various complexing agents such as sodium gluconate, as disclosed in U.S. Pat. No. 4,568,540, glycine, as disclosed in U.S. Pat. Nos. 4,339,432 and 4,425,325, sodium citrate, citric acid, and the like, have been proposed in an attempt to produce relatively stable solutions of zinc chloride.
U.S. Pat. No. 4,568,540 discloses an oral hygiene composition containing a fluoride salt, zinc salt, a buffering agent such as sodium gluconate and a vehicle, having a pH of from about 3.5 to 6.0. Opacified dentifrice formulations are disclosed which contain non-ionic polymer binders such as hydroxyethylcellulose polymers.
The reaction or interaction of zinc compounds of varying solubility with anionic polymers containing carboxylic, sulphonic and/or phosphonic acid functionalities is disclosed in U.S. Pat. No. 4,138,477.
U.S. Pat. No. 4,664,906 discloses oral compositions which exhibit antimicrobial activity containing hexedine and a zinc compound. Opacified gel dentifrices are disclosed which contain sodium gluconate and a non-ionic binder such as hydroxyethyl cellulose.
All of the products derived from these approaches ameliorate oral malodor with varying degrees of effectiveness. The mechanism that has been most often advanced by those skilled in the art for this effect is the ability of the free Zn.sup.+2 to form insoluble salts with nucleophilic compounds, i.e., valeric acid, skatole, indole-3-acetic acid, hydrogen sulfide, mercaptans, and the like, which compounds are typically the cause of oral malodor. All of these substances are respiratory byproducts of the gram-negative (putrefactive) bacteria that are found in the mouth. Once these salts have been formed, they are expectorated with the mouth rinse at once or swallowed with the saliva.
Unfortunately, of the methods noted above, only the lowering of the pH of the zinc chloride solution to less than 4.5 through the use of mineral or organic acid buffers provides well ionized and readily bioavailable zinc ions in a clear, stable solution. This method is unacceptable however, as detailed above.
Some of the weakly complexed zinc compounds resulting from the use of various complexing agents, as noted above, may provide readily available zinc ions, but the formulations suffer from being unstable over time. The stable, strongly complexed or sparingly soluble zinc compounds have only a short term effect against the malodorant chemicals. Once the initial effect has taken place, the remaining unreacted zinc salt or complex is expectorated leaving little or no residual odor control or bacteriostatic effect.
The importance of readily bioavailable zinc is that the cation, once it has entered the oral environment, rapidly adsorbs onto proteins of the oral mucosa and dental pellicle, while simultaneously reacting with oral malodorants. The zinc which does not react immediately will release from the proteinaceous substrate over time, extending its effect significantly. There is also evidence that the retained zinc is bacteriostatic towards gram-negative microbes. The art, however, lacks an aesthetically acceptable composition capable of providing a truly effective amount of bioavailable zinc ions.
U.S. Pat. No. 4,138,477 discloses an oral composition containing a zinc-polymer combination. Suitable zinc compounds include zinc chloride and zinc gluconate. Optionally, the complex can include a dental vehicle containing liquids comprising water and/or a humectant, and solids, comprising carboxymethyl cellulose as a gelling agent. The preferred anionic polymer disclosed is Gantrez.TM., a brand name of a copolymer of maleic anhydride and vinyl methyl ether. This compound is hydrolyzed to form a dicarboxylic acid, which is then complexed with various zinc salts, preferably zinc chloride. The polymer is used in a 4:1 weight ratio with zinc salt, and when adjusted for average carboxyl substitution the zinc to carboxyl group ratio is 1:3. Each zinc ion is capable of being o strongly complexed with the Gantrez.TM. and most likely renders the zinc ion functionally unavailable and therapeutically useless.
The zinc/GantrezT.TM. combination described above has an unacceptably low astringency. Although this lack of astringency may be desirable from an organoleptic viewpoint, it is subjective evidence for the lack of bioavailable zinc ions. Astringency is a side-effect of the zinc ion forming complexes with proteins of the oral mucosa. Attenuation of this effect probably indicates a reduced quantity of available zinc ions. A relatively greater astringency on the other hand would suggest the presence of more available zinc.
U.S. Pat. No. 4,138,477 discloses, at column 2, lines 16-47, that only 53% of the zinc present in the formulations, as measured by equilibrium dialysis, was released after 24 hours, with none being released after 10 minutes or after 1 hour. In the presence of saliva only 7% of the zinc was detected after 24 hours.
Moreover, a release of zinc from the anionic polymer is not induced by exposing the anionic polymer solution to the presence of calcium ions. The relatively more electropositive calcium would be expected to displace the zinc from the polymer, especially in the case where the ionic balance is tenuous. Thus, for at least these reasons it is believed that this zinc/Gantrez.TM. M complex is very strong and most likely renders the zinc ion functionally unavailable.
The art, therefore, lacks a stable and clear aqueous composition of zinc salt, which is truly effective as a mouthrinse and gel dentifrice. A composition having these properties would provide an improved agent for combating the problems of oral malodor, plaque, calculus and periodontal disease.
It is therefore an object of the present invention to provide a stable and clear aqueous composition comprising a zinc compound which provides a source of bioavailable zinc ions from a readily aqueous soluble zinc salt and is useful as a mouth rinse and gel dentifrice for the control of malodor and prevention of calculus.
It is also an object of the present invention to provide an aqueous zinc containing oral formulation having a pH suitably close to oral pH to limit astringency and tartness.
Other objects and aspects of the present invention will become apparent to those skilled in the art from the following description and the appended claims.